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Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation
bioRxiv - Biochemistry Pub Date : 2020-07-27 , DOI: 10.1101/744482
Amélie I. S. Sobczak , Kondwani G. H. Katundu , Fladia A. Phoenix , Siavash Khazaipoul , Ruitao Yu , Fanuel Lampiao , Fiona Stefanowicz , Claudia A. Blindauer , Samantha J. Pitt , Terry K. Smith , Ramzi A. Ajjan , Alan J. Stewart

Zn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. This is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM) and other diseases with an increased risk of developing thrombotic complications. The presence of 5 mol. eq. of myristate, palmitate, stearate, palmitoleate and palmitelaidate reduced Zn2+ binding to HSA. Addition of myristate and Zn2+ increased thrombin-induced platelet aggregation in platelet-rich plasma and increased fibrin clot density and clot time in a purified protein system. The concentrations of key saturated (myristate, palmitate, stearate) and monounsaturated (oleate, vaccinate) NEFAs positively correlated with clot density in subjects with T2DM (and controls). Collectively, these data strongly support the concept that elevated NEFA levels contribute to an increased thrombotic risk in T2DM through dysregulation of plasma zinc speciation.

中文翻译:

血浆非酯化脂肪酸通过改变血浆锌的形态来促进2型糖尿病的凝血能力

Zn 2+是凝血的重要调节剂,可通过人血清白蛋白(HSA)的缓冲作用微调其在血浆中的可用性。HSA转运的非酯化脂肪酸(NEFA)降低​​了其结合/缓冲Zn 2+的能力。这很重要,因为在2型糖尿病(T2DM)和其他疾病中,血浆NEFA的水平升高,形成血栓性并发症的风险增加。存在5摩尔。eq。肉豆蔻酸酯,棕榈酸酯,硬脂酸酯,棕榈油酸酯和棕榈酸锂降低了Zn2 +与HSA的结合。在富含血小板的血浆中添加肉豆蔻酸盐和Zn2 +会增加凝血酶诱导的血小板凝集,并在纯化的蛋白质系统中增加血纤蛋白的凝块密度和凝结时间。患有T2DM的受试者(和对照组)的关键饱和(肉豆蔻酸,棕榈酸酯,硬脂酸酯)和单不饱和(油酸酯,疫苗)NEFA的浓度与血块密度呈正相关。总体而言,这些数据强烈支持这样的概念,即NEFA水平升高会通过血浆锌形态失调而导致T2DM中血栓形成风险增加。
更新日期:2020-07-28
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